Age-related compositional changes and correlations of gut microbiome, serum metabolome, and immune factor in rats.
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ABSTRACT:
SUBMITTER: Zhang X
PROVIDER: S-EPMC8110635 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Age-related changes in human gut microbiota composition have been reported, and such changes might be influenced by the intake of nutrients or diets. To investigate the effects of aging on the gut microbiota independent of nutrient effects, we analyzed the gut microbiomes of 126 micro-pigs at a wide range of ages from newborns to 10 years old. The micro-pigs were reared in a constantly controlled environment. The diversity of the gut microbiome was found to continuously change with age. We also found associations between age and specific members and functions of the gut microbiome. Consistent with previous studies on the human gut microbiome, beneficial microbes including probiotic bacteria and short-chain fatty acid-producers decreased in older pigs, whereas Bacteroides increased with age. Based on the correlation network, Bacteroides seemed to have an important role in determining the relative abundances of other beneficial microbes. Our results suggest that maintaining beneficial gut microbes at a specific ratio corresponding to a certain age might contribute to a younger gut microbiome-age. Furthermore, due to similarities with the human system, micro-pigs are a useful animal model to elucidate the links between aging and the microbiome.
| S-EPMC6925089 | biostudies-literature
Project description:BackgroundLung cancer (LC) is one of the most aggressive, prevalent and fatal malignancies. Gut microbes and their associated metabolites are thought to cause and modulate LC development, albeit influenced by the host genetic make-up and environment. Herein, we identified and classified gut microbiota and serum metabolites associated with LC.MethodsStool samples were collected from 41 LC patients and 40 healthy volunteers. The gut microbiota was analyzed using 16S rRNA gene sequencing. Serum samples were collected from the same LC patients (n=30) and healthy volunteers (n=30) and serum metabolites were analyzed using liquid chromatography-mass spectrometry (LC-MS). Microbiome and metabolome data were analyzed separately and integrated for combined analysis using various bioinformatics methods.ResultsSerum metabolomics uncovered 870 metabolites regulated in 76 metabolic pathways in both groups. Microbial diversity analyses identified 15967 operational taxonomic units (OTUs) in groups. Of these, the abundance of 232 OTUs was significantly different between HC and LC groups. Also, serum levels of glycerophospholipids (LysoPE 18:3, LysoPC 14:0, LysoPC 18:3), Imidazopyrimidines (Hypoxanthine), AcylGlcADG 66:18; AcylGlcADG (22:6/22:6/22:6) and Acylcarnitine 11:0 were substantially different between HC and LC groups. Combined analysis correlated LC-associated microbes with metabolites, such as Erysipelotrichaceae_UCG_003, Clostridium and Synergistes with glycerophospholipids.ConclusionsThere is an intricate relationship between gut microbiome and levels of several metabolites such as glycerophospholipids and imidazopyrimidines. Microbial-associated metabolites are potential diagnostic biomarkers and therapeutic targets for LC.
| S-EPMC8435782 | biostudies-literature
Project description:The interplay between microbiota and host metabolism plays an important role in health. Here, we examined the relationship between age, gut microbiome and host serum metabolites in male C57BL/6J mice. Fecal microbiome analysis of 3, 6, 18, and 28 months (M) old mice showed that the Firmicutes/Bacteroidetes ratio was highest in the 6M group; the decrease of Firmicutes in the older age groups suggests a reduced capacity of gut microflora to harvest energy from food. We found age-dependent increase in Proteobacteria, which may lead to altered mucus structure more susceptible to bacteria penetration and ultimately increased intestinal inflammation. Metabolomic profiling of polar serum metabolites at fed state in 3, 12, 18 and 28M mice revealed age-associated changes in metabolic cascades involved in tryptophan, purine, amino acids, and nicotinamide metabolism. Correlation analyses showed that nicotinamide decreased with age, while allantoin and guanosine, metabolites in purine metabolism, increased with age. Notably, tryptophan and its microbially derived compounds indole and indole-3-lactic acid significantly decreased with age, while kynurenine increased with age. Together, these results suggest a significant interplay between bacterial and host metabolism, and gut dysbiosis and altered microbial metabolism contribute to aging.
| S-EPMC7993679 | biostudies-literature
Project description:Human aging is invariably accompanied by a decline in renal function, a process potentially exacerbated by uremic toxins originating from gut microbes. Based on a registered household Chinese Guangxi longevity cohort (n = 151), we conducted comprehensive profiling of the gut microbiota and serum metabolome of individuals from 22 to 111 years of age and validated the findings in two independent East Asian aging cohorts (Japan aging cohort n = 330, Yunnan aging cohort n = 80), identifying unique age-dependent differences in the microbiota and serum metabolome. We discovered that the influence of the gut microbiota on serum metabolites intensifies with advancing age. Furthermore, mediation analyses unveiled putative causal relationships between the gut microbiota (Escherichia coli, Odoribacter splanchnicus, and Desulfovibrio piger) and serum metabolite markers related to impaired renal function (p-cresol, N-phenylacetylglutamine, 2-oxindole, and 4-aminohippuric acid) and aging. The fecal microbiota transplantation experiment demonstrated that the feces of elderly individuals could influence markers related to impaired renal function in the serum. Our findings reveal novel links between age-dependent alterations in the gut microbiota and serum metabolite markers of impaired renal function, providing novel insights into the effects of microbiota-metabolite interplay on renal function and healthy aging.
| S-EPMC10726799 | biostudies-literature
Project description:ObjectivesPeriodontitis affects the progression of many diseases, while its detailed mechanism remains unclear. This study hopes to provide new ideas for exploring its mechanism by analyzing the gut microbiota and fecal metabolic characteristics of experimental periodontitis rats.MethodsA total of 10 rats were randomly divided into ligature-induced experimental periodontitis (EP) group and healthy control group. After 4 weeks of the experiment, the feces of all rats were collected for sequencing through 16S ribosomal DNA (rDNA) sequencing technology and liquid chromatography-mass spectrometry (LC-MS).Results16S rDNA sequencing results showed that the β-diversity of gut microbiota was significantly different between the EP and control group, and the levels of dominant genera were different. Compared with the control group, Ruminococcus, Escherichia, and Roseburia were significantly enriched in EP, and Coprococcus, Turicibacter, Lachnospira were significantly decreased. Correlation analysis showed that Roseburia exhibited the highest correlation within the genus. Of 3,488 qualitative metabolites, 164 metabolites were upregulated and 362 metabolites were downregulated in EP. Enrichment analysis showed that periodontitis significantly changed 45 positive/negative ion metabolic pathways. Five KEGG pathways, protein digestion and absorption, tyrosine metabolism, glycolysis/gluconeogenesis, niacin and nicotinamide metabolism, and oxidative phosphorylation, are enriched in both the microbiome and metabolome. Correlation analysis showed that the genera with significant differences in periodontitis were usually significantly correlated with more metabolites, such as Roseburia, Lachnospira, Escherichia, Turicibacter, and Ruminococcus. The genera with the same changing trend tended to have a similar correlation with some certain metabolites. In addition, vitamin D2 and protoporphyrin IX have the most significant correlations with microorganisms.ConclusionOur study reveals that periodontitis alters gut microbiota and fecal metabolites. The correlation analysis of microbiota and metabolome provides a deeper understanding of periodontitis, and also provides a direction for the study of periodontitis affecting other diseases.
| S-EPMC9048259 | biostudies-literature
Project description:Vestibular deficit is a very common disorder in clinical practice and is characterized by vertigo, spontaneous nystagmus, and autonomic nervous symptoms, including nausea, vomiting, and sweating. In addition, the comorbidity of vestibular deficit and anxiety has long been an integral component of the medical literature. Previous studies have suggested that the mechanisms underlying this comorbidity involved overlap of vestibular and cerebellar networks. Emerging evidence has shown that the microbiota-gut-brain axis plays a key role in the regulation of affective disorders. Thus, we hypothesized that the gut microbiota may be involved in the comorbidity of vestibular deficit and anxiety. To verify this, we constructed a unilateral labyrinthectomy mouse model to simulate vestibular deficit. Then, 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC-MS) were used to analyze the microbiome and metabolome of the cecal samples collected from mice in the unilateral labyrinthectomy, sham surgery, and control groups. Notably, unilateral labyrinthectomy shaped the composition of the mouse gut microbiome, resulting in increased abundance of Lachnospiraceae NK4A136 group, Odoribacter and Roseburia and decreased abundance of Prevotella and Parasutterella at the genus level. Tax4Fun functional prediction indicated a decrease in tryptophan metabolism in mice in the unilateral labyrinthectomy group. Moreover, functional correlation of changes in gut microbes and metabolites between different groups showed that the oleamide level was negatively correlated with Odoribacter abundance (r = -0.89, p = 0.0002). The butyric acid level was positively correlated with Parasutterella abundance (r = 0.85, p = 0.0010). The propanoate level was negatively correlated with Prevotella abundance (r = -0.81, p = 0.0020). The 20-HETE level was positively correlated with Parasutterella abundance (r = 0.84, p = 0.0013). The altered microbes and metabolites were closely related to the pathogenesis of affective disorders. Our results not only offer novel insights into the vestibular deficit comorbid with anxiety but also build an important basis for future research on this etiology.
| S-EPMC9013912 | biostudies-literature
Project description:Ozone is an asthma trigger. In mice, the gut microbiome contributes to ozone-induced airway hyperresponsiveness, a defining feature of asthma, but the mechanistic basis for the role of the gut microbiome has not been established. Gut bacteria can affect the function of distal organs by generating metabolites that enter the blood and circulate systemically. We hypothesized that global metabolomic profiling of serum collected from ozone exposed mice could be used to identify metabolites contributing to the role of the microbiome in ozone-induced airway hyperresponsiveness. Mice were treated for two weeks with a cocktail of antibiotics (ampicillin, neomycin, metronidazole, and vancomycin) in the drinking water or with control water and then exposed to air or ozone (2 ppm for 3 hours). Twenty four hours later, blood was harvested and serum analyzed via liquid-chromatography or gas-chromatography coupled to mass spectrometry. Antibiotic treatment significantly affected 228 of the 562 biochemicals identified, including reductions in the known bacterially-derived metabolites, equol, indole propionate, 3-indoxyl sulfate, and 3-(4-hydroxyphenyl)propionate, confirming the efficacy of the antibiotic treatment. Ozone exposure caused significant changes in 334 metabolites. Importantly, ozone-induced changes in many of these metabolites were different in control and antibiotic-treated mice. For example, most medium and long chain fatty acids declined by 20-50% with ozone exposure in antibiotic-treated but not control mice. Most taurine-conjugated bile acids increased with ozone exposure in antibiotic-treated but not control mice. Ozone also caused marked (9-fold and 5-fold) increases in the polyamines, spermine and spermidine, respectively, in control but not antibiotic-treated mice. Each of these metabolites has the capacity to alter airway responsiveness and may account for the role of the microbiome in pulmonary responses to ozone.
| S-EPMC6711505 | biostudies-literature
Project description:BackgroundThe oral uptake of nanoparticles is an important route of human exposure and requires solid models for hazard assessment. While the systemic availability is generally low, ingestion may not only affect gastrointestinal tissues but also intestinal microbes. The gut microbiota contributes essentially to human health, whereas gut microbial dysbiosis is known to promote several intestinal and extra-intestinal diseases. Gut microbiota-derived metabolites, which are found in the blood stream, serve as key molecular mediators of host metabolism and immunity.ResultsGut microbiota and the plasma metabolome were analyzed in male Wistar rats receiving either SiO2 (1000 mg/kg body weight/day) or Ag nanoparticles (100 mg/kg body weight/day) during a 28-day oral gavage study. Comprehensive clinical, histopathological and hematological examinations showed no signs of nanoparticle-induced toxicity. In contrast, the gut microbiota was affected by both nanoparticles, with significant alterations at all analyzed taxonomical levels. Treatments with each of the nanoparticles led to an increased abundance of Prevotellaceae, a family with gut species known to be correlated with intestinal inflammation. Only in Ag nanoparticle-exposed animals, Akkermansia, a genus known for its protective impact on the intestinal barrier was depleted to hardly detectable levels. In SiO2 nanoparticles-treated animals, several genera were significantly reduced, including probiotics such as Enterococcus. From the analysis of 231 plasma metabolites, we found 18 metabolites to be significantly altered in Ag-or SiO2 nanoparticles-treated rats. For most of these metabolites, an association with gut microbiota has been reported previously. Strikingly, both nanoparticle-treatments led to a significant reduction of gut microbiota-derived indole-3-acetic acid in plasma. This ligand of the arylhydrocarbon receptor is critical for regulating immunity, stem cell maintenance, cellular differentiation and xenobiotic-metabolizing enzymes.ConclusionsThe combined profiling of intestinal microbiome and plasma metabolome may serve as an early and sensitive indicator of gut microbiome changes induced by orally administered nanoparticles; this will help to recognize potential adverse effects of these changes to the host.
| S-EPMC8941749 | biostudies-literature
Project description:Aflatoxins are a group of potent foodborne toxicants naturally occurring in maize and groundnuts. Differential species-specific sensitivity to aflatoxins has been documented but cannot be fully explained by the differences in metabolism of these toxicants among animal species. Commensal microbial communities (microbiota) are critical to human and animal health, but few studies have assessed interactions between xenobiotic toxins and those microbiota, and its potential effects to humans and animals. Here, an exploratory dosing experiment was conducted to explore effects of Aflatoxin B1 (AFB1) on the gut microbiota in a commonly used rat model. Male F344 rats were randomly divided into groups and treated with different concentrations of AFB1. Microbial communities in fecal samples were assessed using 16S rRNA sequence analysis. We found that samples from the control group had a phylogenetically diverse community, and that increasing AFB1 doses decreased this diversity but increased evenness of community composition. In addition, the gut microbiota from different samples was clustered according to their dosing regimens. There is no community shift at the phylum level but some lactic acid bacteria were significantly depleted by AFB1. These findings suggested that AFB1 could modify the gut microbiota in a dose-dependent manner.
| S-EPMC5009611 | biostudies-literature
Project description:Antibiotic overuse in poultry husbandry poses a potential threat to meat safety and human health. Lauric acid (LA) is a primary medium-chain fatty acid (MCFA) with a strong antibacterial capacity. The goal of this study was to evaluate the beneficial effects of LA on the growth performance, immune responses, serum metabolism, and cecal microbiota of broiler chickens. One-day-old male Ross 308 broilers were randomly divided into 4 groups: CON, fed a basal diet; ANT, a basal diet supplemented with 75 mg/kg antibiotic; LA500, a basal diet supplemented with 500 mg/kg LA; LA1000, a basal diet supplemented with 1000 mg/kg LA. The feeding period was 42 d. The results showed that LA significantly improved broiler growth and immune functions, as evidenced by increased body weight (BW) and average daily gain (ADG), enhanced intestinal mucosal barrier, upregulated immunoglobulins (IgA, IgM, and IgY), and downregulated inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-4, and IL-10) (P < 0.05). HPLC/MS-based metabolome analysis revealed that the serum metabolites in the LA group differed from those of CON and ANT groups. LA markedly decreased the abundance of phosphatidylcholines (PCs), increased lysophosphatidylcholines (LysoPCs), and inhibited the sphingolipid metabolism pathway, indicating its capacity to modulate lipid metabolism. 16S rRNA sequencing indicated that LA significantly altered cecal microbiota composition by reducing Phascolarctobacterium, Christensenellaceae_R-7_group, and Bacteroides, and increasing Faecalibacterium and Ruminococcaceae_UCG-014 (P < 0.05). Furthermore, Spearman correlation analysis revealed that changes in metabolism and microbiota were highly correlated with the growth and immune indices; strong links were also found between lipid metabolism and microbial composition. Taken together, LA promotes broiler growth and immune functions by regulating lipid metabolism and gut microbiota. The above findings highlight the substantial potential of LA as a supplement in poultry diets and provide a new strategy to reduce antibiotic usage and improve food safety.
| S-EPMC8318919 | biostudies-literature